The proposed Center for Transport OncoPhysics (CTO) is a collaborative program among five institutions. The Principal Investigator is Dr. Mauro Ferrari (UTHSC-H) and the Senior Co-Investigator is Dr. Steven Curley (MDACC). Thus, the first overall specific aim of the proposed CTO is to construct a reference system for the understanding of cancer, where the multi-dimensional unit vectors are the differential laws of transport physics across a fundamental set of biobarriers as they present themselves and evolve in tumorigenesis (i.e., transport oncophysics). The second overarching Specific Aim is to demonstrate the therapeutic efficacy of the novel systems and approaches developed within the CTO (multi-stage systems, nanoshuttles, carbon nanotubes, gold colloids, oral administration carriers) in the respective animal models. The proposed CTO will feature: 1. A single scientific framework (transport oncophysics as the differential, and biological barriers as the transport nodes); 2. An integrated multiple multi-scale approach (our mathematics, engineered probes, and imaging instrumentation are all multiscale, and are here employed to study the multiscale architecture of the biological barriers) reflected in shared cores and all project platforms being available to serve as cores for other projects; 3. A dual-intent operational approach, with the engineered transport probes used for basic discovery also being employed for the demonstration of innovative therapeutic modalities addressing unsolved clinical needs in two cancer focus cluster areas; 4. An integrated choice of cancer focus and animal models. The first focus cluster is liver cancer, both primary and metastatic (Projects 1-2), the second is colorectal cancer (Projects 3), with cogent connections being the liver metastasis aspect of colorectal cancer, and the choice of unified animal models that sincerely recapitulate human diseases, under the guidance of Dr. Fidler. Further investigations that address complementary and synergistic aspects of transport onco-physics will be launched throughout the operations of the CTO by means of the Pilot Projects mechanism.